REGULATION OF ABCG2 IN RETINAL STEM CELLS/PROGENITORS

ABCG2 在视网膜干细胞/祖细胞中的调节

• 批准号: 7960550
• 负责人: Sumitra Bhattacharya
• 金额: $ 6.6万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960550
• 关键词: ABCG2 gene; Binding; Cell Differentiation process; Cells; Characteristics; Computer Retrieval of Information on Scientific Projects Database; DNA; Dyes; Fluorescence-Activated Cell Sorting; Funding; Grant; Indium; Institution; Integral Membrane Protein; Maintenance; Mediating; Molecular; Molecular Biology; Phenotype; Population; Regulation; Repression; Research; Research Personnel; Resources; Retinal; Side; Signal Transduction; Small Interfering RNA; Source; Stem cells; System; United States National Institutes of Health; base; in vivo; neurosurgery; notch protein; progenitor; promoter; relating to nervous system; research study; retinal progenitor cell

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the emerging universal characteristics of stem cells/progenitors, including neural and retinal stem cells, is the preferential expression of ABCG2, a half transporter belonging to ATP-binding cassette (ABC) superfamily of transmembrane proteins. These transporters mediate efflux of a broad spectrum of substrates and their ability to preferentially exclude DNA intercalating dye, Hoechst 33342, is regarded to be the molecular basis for the enrichment of stem cells as side population (SP) of cells by fluorescence activated cell sorting. The decline of expression of ABCG2 with retinal differentiation suggests that ABCG2 expression is involved in the maintenance of stem cells, and this has been supported by perturbation of expression by transduction and by siRNA repression, which showed that the magnitude of the SP corresponded to the level of ABCG2 expression and maintenance of stem cell phenotype. We have hypothesized that ABCG2 is regulated through Notch signaling. Our preliminary studies have shown that Notch1 and ABCG2 colocalize, and that inhibition of Notch results in decreased expression of ABCG2 and cell differentiation. We also have evidence that activation of ABCG2 by Notch is mediated through CSL elements in the ABCG2 promotor. These results will be verified by in vivo experiments.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 干细胞/祖细胞（包括神经和视网膜干细胞）的一个新兴的普遍特征是ABCG 2的优先表达，ABCG 2是属于跨膜蛋白的ATP结合盒（ABC）超家族的半转运蛋白。 这些转运蛋白介导广谱底物的外排，并且它们优先排除DNA嵌入染料Hoechst 33342的能力被认为是通过荧光激活细胞分选富集干细胞作为细胞侧群（SP）的分子基础。随着视网膜分化，ABCG 2表达的下降表明ABCG 2表达参与干细胞的维持，并且这已经通过转导和siRNA抑制的表达扰动得到支持，这表明SP的幅度对应于ABCG 2表达水平和干细胞表型的维持。 我们假设ABCG 2是通过Notch信号调节的。 我们的初步研究表明，Notch 1和ABCG 2共定位，并且Notch的抑制导致ABCG 2的表达和细胞分化降低。 我们也有证据表明Notch对ABCG 2的激活是通过ABCG 2启动子中的CSL元件介导的。 这些结果将通过体内实验进行验证。